(a) Field of the Invention
This invention relates to 11(eq)-substituted-2,6-methano-3-benzazocines useful as analgesics and narcotic antagonists.
(b) Description of the Prior Art
2,6-Methano-3-benzazocines substituted in the 11-position with a lower-alkyl group are known. (See for example Gordon et al. U.S. Pat. No. 2,924,603, patented Feb. 9, 1960). Moreover, it is known that compounds in the 5,14-endo-entheno- and ethanotetrahydrooripavine series having ketone, carbinol or lower-alkenyl groups at the 7-position thereof have unusual analgesic potency relative to morphine. [See Bentley et al., J. Am. Chem. Soc. 89, 3267-3292 (1967)]. Consequently there has been much interest in the field of analgesics in incorporating the ketone, carbinol or lower-alkenyl function present in the latter series at the 11-position of 2,6-methano-3-benzazocine-type analgesics, but all synthetic efforts in this direction have previously been unsuccessful.
Certain species of 8-R.sub.2 -9-R.sub.2 '-6(eq)-R.sub.4 -1,2,3,4,5,6-hexahydro-3-R.sub.1 -11(ax)-R.sub.3 -11(eq)-CH.sub.2 Z-2,6-methano-3-benzazocines where R.sub.2 represents a variety of substituents, not including methoxymethoxy; Z represents various ketone functions, CH.sub.2 COR.sub.5, but not including the oxime or carboxymethyloxime thereof, and where R.sub.5 is other than cycloalkyl or either phenyl or phenyl-lower-alkyl substituted in either case in the phenyl ring thereof by a variety of simple substituents; and where Z also represents ##STR1## but not the isomeric group ##STR2## (where R.sub.5 is lower-alkyl and R.sub.6 ' and R.sub.8 are hydrogen or lower-alkyl), are disclosed in my Japanese Patent Appln. 60,111/75, filed May 20, 1975, published Dec. 25, 1975, with corresponding identical disclosure in my U.S. Pat. No. 3,932,422, patented Jan. 13, 1976.